Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas

Glioma Clinical Trial

Official title:

Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas

Clinical Trial Details — Status: Available

Administrative data

• NCT number: NCT04617002
• Other study ID #: ONC028
• Status: Available

Study information

• Verified date: May 2024
• Source: Chimerix
• Contact: Rohinton Tarapore, PhD
• Phone: 1-919-806-1074
• Email: clinicaltrials[@]chimerix.com
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial Summary

This is an intermediate-size expanded access protocol to provide ONC201 (dordaviprone) to patients with H3 K27M-mutant and/or midline gliomas who cannot access ONC201 (dordaviprone) through clinical trials.

Recruitment information / eligibility

• Status: Available
• Enrollment: 0
• Gender: All
• Age group: 0 Years and older

Eligibility

Inclusion Criteria:

1. Patient meets one or more of the criteria below:

Arm A: Closed to further enrollment. Arm B: Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. H3 K27M status does not have to be known or positive for this arm.

Arm C: Patients with primary spinal glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification). Primary spinal glioma must be documented in radiology reporting.

OR Patients with diffuse glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification) AND radiographic evidence of leptomeningeal disease. Leptomeningeal disease must be documented in radiology reporting.

Arm D: Closed to further enrollment. Arm E: Patients with H3 K27M-mutant glioma or midline glioma of unknown H3 K27M mutational status who received ONC201 and/or ONC206 from an alternative (non-Chimerix) source prior to 31 December 2023 as evidenced by documentation (such as pharmacy receipts). Other examples may be confirmed by medical monitor. Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory.

Arm F: Patients with H3 K27M-mutant diffuse glioma or midline glioma with unknown H3 K27M mutational status who have completed frontline radiotherapy prior to 31 December 2023. Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory.

2. Disease Status:

Arm B: Patient is not required to have radiographic or clinical evidence of progressive disease.

Arm C: Patient must have progressive disease as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy.

Arm E: Not Applicable. Arm F: Patient must have progressive disease as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy.

3. Prior Radiotherapy:

Arm B: Patient must be at least 14 days from completion of radiotherapy. Arm C:

Patient must be at least 90 days from completion of radiotherapy and at least 14 days from reirradiation if applicable.

Arm E: Not applicable. Arm F: Patient must be at least 90 days from completion of frontline radiotherapy and at least 14 days from reirradiation if applicable.

4. (Not applicable; criterion removed in Version 5).

5. Patient must weigh at least 10kg.

6. Washouts:

Arm B, C & F: From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies (no washout required for bevacizumab), 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies, and 1 week from devices used to treat cancer.

Arm E: No washouts are required for ONC021 and ONC206. All other anti-cancer agents need to be discontinued prior to enrollment with the exception of bevacizumab.

7. Arm B, C & F: MRI of patient's glioma obtained within 28 days prior to the start of study drug. Arm E: MRI will be obtained within 8 weeks prior to enrollment

8. Adequate organ and marrow function as defined below:

1. Absolute neutrophil count =1,000/mm3 without growth factor use =7 days prior to treatment (Cycle 1 Day 1 [C1D1])

2. Hemoglobin =8.0 mg/dL without red blood cell transfusion =3 days prior to C1D1

3. Total serum bilirubin = 1.5 X upper limit of normal (ULN)

4. AST (SGOT)/ALT (SGPT) =2 X ULN; =5 X ULN if there is liver involvement secondary to tumor.

5. Serum creatinine =1.5 X ULN (OR creatinine clearance =60mL/min/1.73m2) Arm E:

Patients with organ and marrow function values outside the defined criteria must be approved by medical monitor.

9. For patients post pubertal: Female patients must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator.

10. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the patient's age.

Exclusion Criteria:

1. Qualifies for participation in an ongoing ONC201 or ONC206 clinical trial.

2. Arm B, C & F: Previously or current enrollment in an ONC201 clinical study (including open-label and blinded studies) or expanded access protocol or previous exposure to ONC201 from any other source for treatment of CNS tumor.

Arm E: Previous or current enrollment in an ONC201 clinical study (including open-label and blinded studies) or expanded access protocol for the treatment of CNS tumor.

3. Arms B, C, E & F: Current or planned participation in a study of an investigational agent (including ONC206) or using an investigational device.

4. (Not applicable; criterion removed in Version 4).

5. Any known systemic infection that, in the opinion of the investigator, could compromise the safety of the patient while taking ONC201.

6. Prolongation of QT/QTcF interval (QTc interval >480 milliseconds) using Fridericia's QT correction formula on two ECGs separated by at least 2 days.

7. A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome

8. Concomitant use of medication(s) known to prolong the QT/QTc interval.

Related Conditions & MeSH terms

• Glioma
• H3 K27M

Intervention

Drug:
• ONC201 (dordaviprone)
ONC201 (dordaviprone) is a ClpP agonist and DRD2 antagonist.

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	University Cancer & Blood Center	Athens	Georgia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Lurie Children's Hospital	Chicago	Illinois
United States	University of Texas Southwestern	Dallas	Texas
United States	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Miami Cancer Institute	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	New York University Langone - Active, Enrolling	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	University of Nebraska Medical Center - Adults Only	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	BMDACC at Banner University Medical Center Phoenix	Phoenix	Arizona
United States	Providence Neurological Specialties Clinic	Portland	Oregon
United States	University of Rochester	Rochester	New York
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	Providence Saint John's Health Center	Santa Monica	California
United States	Overlook Medical Center/ Atlantic Health System	Summit	New Jersey
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Chimerix

Country where clinical trial is conducted

United States,